We are trying to understand why certain HIV isolates enter and infect some cell types but not others. For example, some HIV isolates are able to infect primary T cells, while others are able to infect both primary T cells and macrophages; some isolates have the capacity to induce the formation of large multinuclear cells (syncytia) while others cannot. Furthermore, we have found that certain viruses can alter their biological characteristics by passage in tissue culture, and the genetic changes that permit this to occur are in the HIV envelope, the protein involved in the initial binding and uptake of the virus. Thus, part of the understanding of HIV tropism involves understanding the biochemical events involved in virus binding and uptake. Because binding and entry is not the whole story of viral tropism, we are investigating determinants of tropism in other regions of the viral genome. Our work involves using assays to measure virus growth, virus amounts, and virus neutralization. A familiarity with these assays and methods is important to the FDA review process, where such assays are used to ascertain the efficacy of vaccines against HIV.